Consistently in the previous studies the ethanol treatment impaired learning and memory, upregulated dynorphins and increased glutamate overflow in the CA3 region. The critical finding of the present study (paper submitted to Biological Psychiatry) was that the highly selective long-acting KOR-antagonist nor-BNI administered after cessation of ethanol exposure reversed cognitive deficits and normalized elevated glutamate levels in ethanol-treated rats. Nor-BNI was effective under both systemic or intra-hippocampal administration suggesting that ethanol actions on glutamate overflow and spatial memory were mediated through the hippocampal dynorphin-KOR-dependent mechanism. No effects of nor-BNI on learning and memory and glutamate levels were evident in nave animals suggesting that this mechanism is not activated under normal conditions. These findings suggest that impairments of spatial learning and memory by binge-like ethanol exposure are mediated through the KOR&#61472;activation by upregulated dynorphins resulting in elevation in glutamate levels. Selective KOR&#61472;antagonists may correct alcohol-induced pathological processes, thus representing a novel pharmacotherapy for treating of ethanol-related cognitive deficits.